Frank Braatz

Reduced reactivation from dormancy but maintained lineage choice of human mesenchymal stem cells with donor age.

Mesenchymal stem cells (MSC) are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5–80 years) were characterized regarding colony-forming unit-fibroblast (CFU-F) numbers, single cell cloning efficiency (SSCE), osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP) activity, mineralization, Oil Red O content, proteoglycan- and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. Conclusion: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individuals.

Kinematics and kinetics with an adaptive ankle foot system during stair ambulation of transtibial amputees

Conventional prosthetic feet cannot adapt to specific conditions such as walking on stairs or ramps. Amputees are therefore forced to compensate their prosthetic deficits by modifying the kinematics and kinetics of their lower limbs. The Proprio-Foot (Ossur) intends to reduce these compensation mechanisms by automatically increasing dorsiflexion during stair ambulation thanks to an adaptive microprocessor-controlled ankle. The present investigation proposes to analyze the biomechanical effects of the dorsiflexion adaptation in transtibial (TT) amputees during stair ambulation. Sixteen TT amputees and sixteen healthy controls underwent conventional 3D gait analysis. Kinematics and kinetics of the lower limbs were compared during stair ascent and descent performed by patients with the prosthetic foot set to a neutral ankle angle and with an adapted dorsiflexion ankle angle of 4 degrees . Norm distance as well as minimum and maximal values of sagittal kinematics and kinetics were calculated for comparisons between patients and control subjects. For both stair ascent and descent, an improvement of the knee kinematics and kinetics could particularly be noticed on the involved side with an increase of the knee flexion and an increase of the knee moment during stance. Therefore, despite its additional weight compared to a conventional prosthetic ankle, the Proprio-Foot should be beneficial to active TT amputees whose knee musculature strength does not constitute a handicap.

Long-Term Results After Gastrocnemius-Soleus Intramuscular Aponeurotic Recession as a Part of Multilevel Surgery in Spastic Diplegic Cerebral Palsy

BACKGROUND Equinus of the foot at the ankle is one of the most common deformities in patients with spastic diplegic cerebral palsy, leading to gait disturbances and secondary deformities. During single-event multilevel surgery, equinus is commonly corrected by calf muscle lengthening, such as gastrocnemius-soleus intramuscular aponeurotic recession. Various studies have described satisfactory short-term results after gastrocnemius-soleus intramuscular aponeurotic recession. However, there is no evidence for maintenance of equinus correction because of the small and heterogeneous case series and short follow-up time previously reported. METHODS The present study provides long-term results after gastrocnemius-soleus intramuscular aponeurotic recession as a part of multilevel surgery for the treatment of equinus in forty-four patients with spastic diplegia who were able to walk (forty-eight legs had lengthening of the gastrocnemius and thirty-four legs had lengthening of the gastrocnemius and soleus). Standardized three-dimensional gait analysis and clinical examination were done preoperatively and at one year, a mean (and standard deviation) of 3 ± 1 years, and a mean of 9 ± 2 years after surgery. RESULTS Significant improvements in kinematic and kinetic ankle parameters on gait analysis as well as passive dorsiflexion in clinical examination were found one year after surgery. While there was a significant loss of passive dorsiflexion at the time of long-term follow-up, the improvements in gait analysis parameters were maintained. The endurance of gait improvements was accompanied by a persistent increase of dorsiflexor muscle strength without relevant loss of plantar flexor strength. Although it was not significant, there was a tendency for deterioration of gait analysis parameters over the nine years. The analysis of individual patterns showed recurrence of equinus at the ankle in 24% of the legs. Early-onset calcaneal gait was found one year after surgery in seven legs (9%), but without secondary crouch gait, and there was recovery at the time of the long-term follow-up. Late-onset calcaneal gait was seen at the time of long-term follow-up in eight legs (10%), of which four had an accompanying crouch gait. CONCLUSIONS Gastrocnemius-soleus intramuscular aponeurotic recession as a part of multilevel surgery leads to satisfactory correction of mild and moderate equinus deformity in children and adolescents with spastic diplegia without relevant risk for overcorrection and should be preferred over Achilles tendon lengthening to avoid overlengthening. The long-term results in the present study demonstrate that the improvements are long-lasting on average, but individual patients tend to develop recurrence and may need secondary gastrocnemius-soleus intramuscular aponeurotic recession.

Development of Knee Function After Hamstring Lengthening as a Part of Multilevel Surgery in Children with Spastic Diplegia: A Long-term Outcome Study

BACKGROUND Hamstring lengthening commonly is performed for the treatment of flexed knee gait in patients with spastic diplegic cerebral palsy. Satisfactory short-term results after hamstring lengthening have been demonstrated in various studies. However, evidence for the effectiveness of hamstring lengthening to correct flexed knee gait is scant because of small and inhomogeneous case series, different surgical techniques, and short follow-up. METHODS The long-term results for thirty-nine patients with spastic diplegia and flexed knee gait who were managed with intramuscular hamstring lengthening as a part of multilevel surgery are presented. Standardized three-dimensional gait analyses and clinical examinations were performed for all patients preoperatively and at one, three, and six to twelve years postoperatively. RESULTS Significant improvements in kinematic parameters and the popliteal angle were noted at short-term follow-up (p < 0.01), supporting the results of previous studies. Long-term results showed significant deterioration of minimum knee flexion in stance and the popliteal angle (p < 0.01), whereas the improvements in the Gross Motor Function Classification System and Gillette Gait Index were maintained. This recurrence of flexed knee gait is partial and measurable. Increased pelvic tilt was found in 49% of the limbs postoperatively, which may represent one factor leading to recurrence of flexed knee gait. Genu recurvatum was seen in eighteen patients (twenty-seven limbs; 35%) one year postoperatively, especially in the patients with a jump knee gait pattern preoperatively. At long-term follow-up, genu recurvatum resolved in many limbs, but 12% of the limbs showed residual genu recurvatum, indicating that overcorrection represents a problem following hamstring lengthening. CONCLUSIONS The results of the present study are crucial for the prognosis of knee function after hamstring lengthening as a part of multilevel surgery. Recurrence and possible overcorrection should be considered in treatment planning.

Pressure characteristics at the stump/socket interface in transtibial amputees using an adaptive prosthetic foot.

BACKGROUND The technological advances that have been made in developing highly functional prostheses are promising for very active patients but we do not yet know whether they cause an increase in biomechanical load along with possibly negative consequences for pressure conditions in the socket. Therefore, this study monitored the socket pressure at specific locations of the stump when using a microprocessor-controlled adaptive prosthetic ankle under different walking conditions. METHODS Twelve unilateral transtibial amputees between 43 and 59 years of age were provided with the Proprio-Foot (Ossur) and underwent an instrumented 3D gait analysis in level, stair, and incline walking, including synchronous data capturing of socket pressure. Peak pressures and pressure time integrals (PTI) at three different locations were compared for five walking conditions with and without using the devices ankle adaptation mode. FINDINGS Highest peak pressures of 2.4 k Pa/kg were found for incline ascent at the calf muscle as compared to 2.1 k Pa/kg in level walking with large inter-individual variance. In stair ascent a strong correlation was found between maximum knee moment and socket pressure. The most significant pressure changes relative to level walking were seen in ramp descent anteriorly towards the stump end, with PTI values being almost twice as high as those in level walking. Adapting the angle of the prosthesis on stairs and ramps modified the pressure data such that they were closer to those in level walking. INTERPRETATION Pressure at the stump depends on the knee moments involved in each walking condition. Adapting the prosthetic ankle angle is a valuable means of modifying joint kinetics and thereby the pressure distribution at the stump. However, large inter-individual differences in local pressures underline the importance of individual socket fitting.

Long-term outcome of femoral derotation osteotomy in children with spastic diplegia

Satisfactory short-term results after femoral derotation osteotomy (FDO) for the treatment of internal rotation gait in cerebral palsy have been reported by various authors. However, there are only a few longer-term studies reporting results 5 years after FDO and these are not in agreement. There are no reports on the clinical course beyond the pubertal growth spurt. 33 children with diplegia (n=59 legs, age: 10.5±3.6 years) and internally rotated gait were examined pre- (E0), 1 year (E1), 3±1 (E2) and 9±2 (E3) years after distal (27 legs) or proximal (32 legs) FDO as part of multilevel surgery, using standardized clinical exam and 3D gait-analysis at all examinations. The amount of intra-operative derotation averaged 25°. ANOVA was used for statistics (p<0.05). Mean hip internal rotation in stance at E0 of 17.3° was significantly changed to 1.0° of external rotation at E1 and was maintained at 4.2° at E3. The same clinical course was found for foot progression angle. The mid-point of passive hip rotation at E0 was 21°. This was significantly decreased to 6° at E1 and showed a small but significant increase reaching 12° at E3. The results of this study showed a good overall correction of internally rotated gait following FDO. These improvements were maintained at long-term follow-up after the pubertal growth spurt. Recurrence was observed in some cases with overall severe deterioration. In those patients persistent dynamic factors leading to recurrence should be further investigated.

Long-Term Results After Distal Rectus Femoris Transfer as a Part of Multilevel Surgery for the Correction of Stiff-Knee Gait in Spastic Diplegic Cerebral Palsy

BACKGROUND The evidence for distal rectus femoris transfer as a part of multilevel surgery for the correction of stiff-knee gait in children with spastic diplegic cerebral palsy is limited because of inconsistent outcomes reported in various studies and the lack of long-term evaluations. METHODS This study investigated the long-term results (mean, nine years) for fifty-three ambulatory patients with spastic diplegic cerebral palsy and stiff-knee gait treated with standardized distal rectus femoris transfer as a part of multilevel surgery. Standardized three-dimensional gait analysis and clinical examination were carried out before surgery and at one year and nine years after surgery. Patients with decreased peak knee flexion in swing phase who had distal rectus femoris transfer to correct the decreased peak knee flexion in swing phase (C-DRFT) were evaluated separately from those with normal or increased peak knee flexion in swing phase who had distal rectus femoris transfer done as a prophylactic procedure (P-DRFT). RESULTS A significantly increased peak knee flexion in swing phase was found in the C-DRFT group one year after surgery, while a significant loss (15°) in peak knee flexion in swing phase was noted in the P-DRFT group. A slight but not significant increase in peak knee flexion in swing phase in both groups was noted at the time of the long-term follow-up. A significant improvement in timing of peak knee flexion in swing phase was only found for the C-DRFT group, and was maintained after nine years. Knee motion and knee flexion velocity were significantly increased in both groups and were maintained at long-term follow-up in the C-DRFT group, while the P-DRFT showed a deterioration of knee motion. CONCLUSIONS Distal rectus femoris transfer is an effective procedure to treat stiff-knee gait featuring decreased peak knee flexion in swing phase and leads to a long-lasting increase of peak knee flexion in swing phase nine years after surgery. Patients with more involvement showed a greater potential to benefit from distal rectus femoris transfer. However, 18% of the patients showed a permanently poor response and 15% developed recurrence. In patients with severe knee flexion who underwent a prophylactic distal rectus femoris transfer, a significant loss in peak knee flexion in swing phase was noted and thus a prophylactic distal rectus femoris transfer may not be indicated in these patients. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Gait analysis may help to distinguish hereditary spastic paraplegia from cerebral palsy

Hereditary spastic paraplegia (HSP) designates a group of genetic disorders typically leading to spasticity in the lower limbs and consequently to gait disorders. Although the symptoms are similar to those of cerebral palsy (CP), the correct diagnosis is important for treatment recommendations as one condition is progressive in nature whereas the other is not. Due to the heterogeneity of HSP, genetic testing is complex and in some genetic forms still not possible. The aim of this study was, therefore, to investigate if instrumented 3D-gait analysis could help distinguish between these two conditions. The gait pattern of 29 patients with HSP was compared with that of 29 patients with CP who were matched in age, sex, and the extent of gait disturbance and also to 29 typically developing subjects for reference. More than 3000 gait parameters were evaluated for their relevance to classify patients into diagnostic groups. Cluster analysis revealed that these gait features may classify only subgroups of symptoms as the gait pattern is very heterogeneous within each diagnosis group. However, prolonged hip extension, knee extension, and ankle plantar flexion were identified as indicators for HSP. In addition, large trunk tilt velocities appear unique in some cases of HSP. These indicators in gait pattern may contribute in establishing the diagnosis of HSP, which is important in predicting outcome when planning surgical treatment for functional improvements in these patients.

Motion capture of the upper extremity during activities of daily living in patients with spastic hemiplegic cerebral palsy

Investigations using motion capture to analyze limitations in range of motion (ROM) of the upper extremity in adults with cerebral palsy (CP) are scarce. To evaluate the influence of those limitations on activities of daily living (ADL) and to determine potential mechanisms of compensation, we investigated 15 adults with hemiplegic CP using motion capture while they performed 10 defined ADLs. Data from the nonaffected body side and those from an age-matched able-bodied group were also collected and compared with our subjects. We measured motion of the elbow, shoulder, and trunk and found significant differences in ROM at these sites. The most pronounced reduction in ROM was observed distally in supination and pronation of the elbow. Here, the affected body side of the adults showed a reduction in supination of 45° compared to the able-bodied group. Furthermore we found a correlation between the Manual Ability Classification System (MACS) and the limitations in ROM. In summary, adults with spastic, hemiplegic CP show limitations in ROM accentuated distally during ADLs. The MACS gives conclusive information about those limitations.

Autologous capping during resection arthroplasty of the hip in patients with cerebral palsy

In patients with severe quadriplegic cerebral palsy and painful hip dislocation proximal femoral resection arthroplasty can reduce pain, but the risk of heterotopic ossification is significant. We present a surgical technique of autologous capping of the femoral stump in order to reduce this risk, using the resected femoral head as the graft. A retrospective study of 31 patients (43 hips) who had undergone proximal femoral resection arthroplasty with (29 hips) and without autologous capping (14 hips) was undertaken. Heterotopic ossification was less frequent in patients with autologous capping, and a more predictable pattern of bony overgrowth was found. For a selected group of non-ambulatory patients with long-standing painful dislocation of the hip, we recommend femoral resection arthroplasty over more complicated reconstructive operations. The risk of heterotopic ossification, which is a major disadvantage of this operation, is reduced by autologous capping.